Magnesium hydroxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-04-13 to 2010-06-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Magnesium hydroxide

EC Number:

215-170-3

EC Name:

Magnesium hydroxide

Cas Number:

1309-42-8

Molecular formula:

H2MgO2

IUPAC Name:

magnesium dihydroxide

Specific details on test material used for the study:

- Name of the test material used in the report: Magnesium hydroxide
- Appearance: white powder
- Batch No.: 20BR0026
- Purity: 99.90%
- Storage: at room temperature in the dark
- Expiry date: 2012-01-31

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 8 weeks approx.
- Weight at study initiation: Body weight variation of selected animals did not exceed +/- 20% of the sex mean
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages containing sterilised sawdust as bedding material
- Diet: Pelleted rodent diet was available ad libitum
- Water: Ad libitum
- Acclimation period: Not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 - 21.5 °C
- Humidity (%): 34 - 60 %
- Photoperiod (hrs dark / hrs light): 12 hours dark and 12 hours light

IN-LIFE DATES: From: 13th April 2010 To: 29th April 2010

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Standard vehicle for use in testing


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Limit test

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 female animals per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortaility/viability twice daily. Body weights were measured on day 1 (pre-administration), day 8 and day 15.
- Necropsy of survivors performed: Yes.
- Other examinations performed: Clinical signs were observed at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.

Statistics:

Not required

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred (see Table 1).

Clinical signs:

other: Hunched posture and/or piloerection was noted among all animals on Day 1 (see Table 2).

Other findings:

Macroscopic findings:
No abnormalities were found at macroscopic post mortem examination of the animals ( see Table 4).

Any other information on results incl. tables

Table 1: Mortality Rate

Test day

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Hours after treatment

0

2

4

Females 2000 MG/KG

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Females 2000 MG/KG

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

 Key: X= no signs observed

 Table 2: Clinical Signs

Test day

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Hours after treatment

Max grade

0

2

4

Females 2000MG/KG Animal 1

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Skin/fur Piloerection

(1)

X

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Animal 2

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Animal 3

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Females 2000 MG/KG  Aniaml 4

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Skin/fur piloerection

(1)

X

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Animal 5

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Skin/fur piloerection

(1)

X

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Animal 6

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Skin/fur piloerection

(1)

X

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Key: X= no signs observed

√=signs observed

Table 3: Body Weights (Gram)

Sex/Dose	Animal	Day 1	Day 8	Day 15
Females 2000 MG/KG
	1	149	175	189
	2	151	180	192
	3	146	174	189
	Mean	149	176	190
	St. Dev	3	3	2
	N	3	3	3
	4	155	179	196
	5	153	174	188
	6	161	185	194
	Mean	156	179	193
	St.Dev	4	6	4
	N	3	3	3

 

Table 4: Macroscopic Findings

Animal Organ	Finding	Day of Death
Females 2000 Mg/Kg
1	No Findings Noted	Scheduled necropsy Day 15 after treatment
2	No Findings Noted	Scheduled necropsy Day 15 after treatment
3	No Findings Noted	Scheduled necropsy Day 15 after treatment
Females 2000 Mg/Kg
4	No Findings Noted	Scheduled necropsy Day 15 after treatment
5	No Findings Noted	Scheduled necropsy Day 15 after treatment
6	No Findings Noted	Scheduled necropsy Day 15 after treatment

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study in rats conducted according to OECD 423, no mortality occurred at the dose level 2000 mg/kg bw. Hence, the LD50 was determined to exceed 2000 mg/kg body weight.

Executive summary:

In an acute oral toxicity study conducted according to OECD 423, groups of female Wistar rats (3 per group) were given a single dose of magnesium hydroxide (purity 99.9%) diluted in water at a dose of 2000 mg/kg bw. Animals were observed for 14 days.

No mortality occurred. Hunched posture and/or piloerection was noted among all animals on Day 1. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals.

Based on the results from this study, the oral LD50 value in rats is considered to be > 2000 mg/kg bw.